Studies are being designed to determine which of the major classes of hepatic cells (parenchymal, endothelial and Kupffer) are responsible for the uptake of different lipoproteins by the liver and to define which apoproteins mediate the uptake of lipoproteins by the different cell types. To facilitate the generation of suspensions of hepatic cells for these studies rat livers are perfused in situ with a solution of collagenase. The basic technique has been modified by including in the perfusate soybean trypsin inhibitor to reduce tryptic damage to cell surface receptors and deoxyribonuclease to inhibit DNA-mediated aggregation of cells. A method has been developed to separate gently endothelial and Kupffer cells from erythrocytes and parenchymal cells which involves Percoll gradient centrifugation. Endothelial cells are separated from Kupffer cells by centrifugal elutriation. The degree of separation achieved appears to be satisfactory as judged by selective stains for Kupffer cells (e.g. tartrate resistant acid phosphatase and endogenous peroxidase). The viability of cell preparations is being assessed by measuring cell membrane potentials. The first ligand to be used in these studies is radiolabeled human low density lipoprotein.